This proposal is to support the candidate, Roy M. Gulick, MD, MPH, Associate Professor of Medicine and the Director of the Cornell HIV Clinical Trials Unit, as an HIV/AIDS clinical researcher. Dr. Gulick has conducted clinical trials in HIV-infected patients since 1989, with a focus on antiretroviral therapy studies. His long-term career goals are to design, conduct, and analyze high-quality research to address clinically important questions in the treatment of patients with HIV/AIDS and to teach and mentor trainees to help develop their careers as clinical investigators. The specific aims of the proposal are: (1) to compare three simple protease inhibitor (PI)-sparing regimens in HIV-infected, treatment-naive patients: zidovudine/ lamivudine with either (a) the non-nucleoside reverse transcriptase inhibitor (NNRTI), efavirenz; (b) the nucleoside reverse transcriptase inhibitor (nRTI), abacavir; or (c) the combination of efavirenz and abacavir; (2) (a) to evaluate and compare the safety, pharmacokinetics, and antiretroviral activity of four dose levels of T-1249, an investigational HIV fusion inhibitor; and (b) to design and implement a pilot study of dual HIV entry inhibitors; (3) to study an HIV gag DNA vaccine in HIV-infected patients with CD4 cell counts >500/mm3 and virologic suppression on a potent antiretroviral regimen; and (4) to assist in the planning, design and conduct of antiretroviral therapy studies in Haiti. The specific aims will be accomplished by designing, conducting, and analyzing clinical trials of both antiretroviral therapies and immune-based therapies, and by teaching and mentoring trainees from Weill Medical College of Cornell University and developing a training program for prospective investigators from developing countries, such as Haiti. Clinical trials of novel drugs and strategies will improve the treatment of HIV-infected patients, both in the United States and the developing world. Effective mentoring and training will help develop future clinical investigators.